1. Field
The present invention relates to use of a sesquiterpenoid-based compounds having an estrogenic activity or a pharmaceutically acceptable salt thereof, or extracts of Cyperus rotundus comprising the same or a fraction thereof in the prevention and treatment of menopausal disease.
2. Description of Related Art
As women get older, ovarian functions deteriorate, ovulation and production of female sex hormones eventually stop. Menopause is usually diagnosed by the absence of menstruation for 1 year. Typically, these changes occur in the mid-to-late 40s, and gradually progress. A term for about 1 year after onset of menopause at which menstruation stops completely is called menopausal transition, more often, climacterium. It lasts for about 4˜7 years on average. Menopause, itself, occurs as a result of ovarian aging, and menopause, rather than being an illness, is a natural change in the body. A Menopausal disorder is caused by a decline in the level of estrogen, a female hormone having various functions of helping blood circulation, body weight regulation, bone maintenance as well as female sexual characteristics around the age of 50 in the climacteric period. It is known that the same symptoms also occur in estrogen-deficient patients due to other causes such as oophorectomy or decline in ovarian functions, besides climacterium.
A menopausal disorder causes neuropsychiatric symptoms such as poor concentration, insomnia, headache, tinnitus, nervousness, etc., as well as changes in the body such as abdominal obesity, atrophy of uterus, cognitive impairment, blood flow disorder, skin aging, etc., and therefore, it is a main cause of reducing quality of life. With a growing population of post-menopausal women, their cardiovascular diseases and osteoporosis have been prevented and treated by a hormone replacement therapy using female hormones, estrogen and progestin. However, long-term use of the hormone replacement therapy may cause adverse effects including risk of breast cancer. Therefore, the hormone replacement therapy used for severe menopausal diseases should be implemented considering the possibility of various complications. For this reason, phytoestrogens have been attempted in some cases, but their efficacies are weaker than that of estrogen, and may induce breast cancer upon excessive exposure thereto. Accordingly, there has been demand to develop phytoestrogens capable of exhibiting estrogenic effects, thereby preventing or treating menopausal disorders, while showing no excessive effects, thereby reducing the risk of breast cancer.
Meanwhile, allergy is a biochemical phenomenon showing a specific and altered reaction against a foreign substance. During allergic reaction, various cytokines are released to cause allergy-specific symptoms. In this regard, the allergy-producing substances are called allergens. The etiology of allergy is a pathological process in the body resulting from antigen-antibody reaction, and allergy is generally classified into 1 of 4 types according to time taken for the reaction and complement mediation.
During allergic reaction, IgE is produced from B-cells by a helper T-cell which has already become activated by a foreign antigen presented by a macrophage, and IgE thus produced binds to a high-affinity IgG receptor (FcRIa) on a mast cell membrane. Cross-linking between antigens such as ticks or pollens and a plurality of the bound IgE antibodies triggers receptor aggregation, and mast cells are activated by the cross-linking and aggregation. An increase in cytosolic calcium ion (Ca2+) levels in the activated mast cells causes degranulation. In turn, degranulation causes the release of chemical transmitters such as histamine from mast cells and the release of prostaglandin, leukotriene, etc. which are newly synthesized, at the same time. The chemical transmitters released by degranulation include NCF (neutrophil chemotactic factor), ECF (eosinophil chemotactic factor), and PAF (platelet activating factor) which act as chemotactic factors of inflammatory cells such as eosinophils, neutrophils, etc. in addition to histamine having functions of arteriolar dilation, increased capillary permeability, contraction of bronchial smooth muscle, or secretion enhancement, serotonin, and leukotriene. Allergic reaction is mediated by theses chemical transmitters.
A therapeutic or prophylactic agent for allergy is largely divided into a steroidal anti-inflammatory agent or a nonsteroidal anti-inflammatory agent and antihistamines or antileukotrienes. The former has a strong immunosuppressive action showing a temporary sedative effect within a short period of time, but its long-term use generates many problems from mild side-effects such as nausea, to severe side-effects such as growth inhibition or osteoporosis. The latter can show a temporary sedative effect, but its use is restricted because of side-effects of sleepiness, dizziness, etc. Therefore, studies have been actively conducted to develop compounds enabling safe applications with high efficacies and effects.
The present inventors have made many efforts to investigate a substance capable of exhibiting an estrogenic activity and/or an anti-allergic activity with fewer side-effects. As a result, they investigated a sesquiterpenoid compound showing an estrogenic activity or an anti-allergic activity from an extract of Cyperus rotundus. They found that this sesquiterpenoid compound is an estrogen agent having fewer side-effects, and has an advantage of being used for the prevention or treatment of menopausal disorders. They also investigated an extract of Cyperus rotundus and a fraction thereof which includes the above compound to show excellent estrogenic activity and/or the anti-allergic activity, and they found that the compound or the extract of Cyperus rotundus comprising the compound, and the fraction thereof can be used for the prevention and treatment of menopausal disorders or allergic diseases, thereby completing the present invention.